Synthesis of (E)‐2‐Alkenylazaarenes via Dehydrogenative Coupling of (Hetero)aryl‐fused 2‐Alkylcyclic Amines and Aldehydes with a Cobalt Nanocatalyst

Abstract

To date, the synthesis of (E)‐2‐alkenylazaarenes via the condensation of 2‐methyl N‐heteroarenes with aldehydes or their equivalents has been well demonstrated. However, the direct formation of such a class of useful compounds from extensively distributed 2‐alkylcyclic amine motifs remains an unresolved goal. Herein, by employing the nitrogen‐silica‐doped carbon (Vulcan XC‐72R) as the support, we have developed a low‐loading cobalt nanocatalyst (Co/N‐Si‐C). The combination of such a catalyst with p‐nitrobenzoic acid and molecular O2 exhibits excellent catalytic performance towards the dehydrogenative coupling of (hetero)aryl‐fused 2‐alkylcyclic amines with aldehydes to afford the (E)‐2‐alkenylazaarenes. In the reaction, effective capture of the partially dehydrogenated cyclic amine motifs appears to be the key strategy to address the issue of the chemoselectivity. The developed catalytic transformation proceeds with the merits of broad substrate scope, good functional group tolerance, high atom‐efficiency, use of an earth‐abundant and reusable cobalt catalyst and molecular O2 as a green oxidant, which offers an important basis for the direct conversion of inert cyclic amine units into the functional frameworks.

Co-N-Si/AC Catalyst for Aerobic Oxidation of Benzyl Alcohols to Esters under Mild Conditions

“…Therefore, the exploration and development of efficient catalytic systems for oxidative esterification under mild conditions are of increasing interest in both green chemistry and organic synthesis. Continuous effort has gone into research in the conversion of plentiful and sustainable alcohol resources into functional molecules [23][24][25][26][27][28] and the exploitation of heterogeneous base metal catalysts as well as the catalytical oxidant performance of related heterogeneous catalysts [29][30][31][32][33]. The natural amplitude of cobalt and its excellent performance in the oxidation reaction [34][35][36] as well as the capacity of silicon dioxide in regulating the micropore size of carbon material to facilitate mass transfer have been observed [37][38][39].…”

α‐Chymotrypsin–catalyzed direct C (Sp3)–H functionalization reactions for synthesis of azaarene derivatives in water

“…Azaarene derivatives act as important intermediates in many industrial processes, and one of the most efficient methods for their synthesis is the direct C (sp 3 )–H functionalization of alkyl‐substituted pyridines and quinolines. In 2018, Zhou et al developed a low‐loading cobalt nanocatalyst using nitrogen‐silica–doped carbon as the support. The combination of such a catalyst with 4‐nitrobenzoic acid and molecular O 2 exhibits excellent catalytic performance toward the dehydrogenative coupling of (hetero)aryl‐fused 2‐alkylcyclic amines with aldehydes to afford the (E)‐2‐alkenylazaarene.…”

Iron-Catalyzed Coupling of Methyl N-Heteroarenes with Primary Alcohols: Direct Access to E-Selective Olefins

“…In this direction, recently we developed a couple of nickel-catalyzed novel protocols for the synthesis of secondary amines, amides, including interesting N -heterocycles . Most recently, we and others have also developed the alkylation of methyl substituted N -heteroarenes with alcohols. − , Recent studies for α-olefination of alkylazaarenes with primary alcohols has been developed using manganese pincer catalysts. , Notably, such pincer complexes employed expensive ligands systems based on PN 5 P or NNN core and required multistep synthesis (Scheme c).…”

“…Nevertheless, in the presence of Fe catalyst, 2a and 2a′ resulted in 52% and 21% yield of 3a , whereas a control experiment involving a mixture of 2a′ and 2b with 1a under the standard conditions gave 40% yield of 3a (Scheme ). We believe that, in the presence of an aldehyde, Fe catalyst might form an adduct with the enamine 1a′ , which partially retarded the dearomatization process and resulted diminished product conversion …”

“…On the basis of the control experiments, a plausible mechanism is depicted in Scheme . Indeed, in the absence of base, we did not observe any 3a (Table , entry 13), emphasizing the potential role of t -BuOK for (de)­aromatization of quinaldine 1a to 1a′ (Scheme ).…”